D-4F Ameliorates Contrast Media-Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway.
D-4F Ameliorates Contrast Media-Induced Oxidative Injuries in Endothelial Cells via the AMPK/PKC Pathway.
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D-4F 通过 AMPK/PKC 途径改善造影剂诱导的内皮细胞氧化损伤
DOI：
10.3389/fphar.2020.556074
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发表时间：
2020
影响因子：
5.6
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Guo Y;Li W;Qian M;Jiang T;Guo P;Du Q;Lin N;Xie X;Wu Z;Lin D;Liu D
血管内皮细胞功能障碍参与了造影剂(CM)致急性肾损伤(CI-AKI)血管造影或介入治疗后的病理生理过程。先前的研究发现，载脂蛋白A-I(apoA-I)模拟肽D-4F通过上调血红素加氧酶-1(HO-1)的表达和清除过量产生的活性氧(ROS)来减轻内皮损伤。然而，D-4F是否可以通过抑制ROS的产生来减轻内皮细胞的氧化损伤仍不清楚。本研究选择了一种具有代表性的非离子碘化CM--碘化甘油醇进行体外和体内研究。用显微照相、乳酸脱氢酶(LDH)活性和细胞计数试剂盒8(CCK-8)检测内皮细胞活性。通过流式细胞仪分析和caspase-3活化检测细胞凋亡。通过单核细胞黏附实验和黏附分子表达检测内皮细胞的炎症反应。通过硫代巴比妥酸反应物质(TBARS)测定脂质过氧化产物丙二醛(MDA)的生成来检测ROS的产生。用3-硝基酪氨酸酶联免疫吸附试验试剂盒检测过氧亚硝酸根(ONOO-⁻)的形成。碘黄醇可损伤人脐静脉内皮细胞的活力，促进血管细胞黏附分子-1和细胞间黏附分子-1的表达，并诱导细胞凋亡。然而，D-4F减轻了这些伤害。此外，碘诱导蛋白激酶CβII、P47、RAC1和内皮型一氧化氮合酶(ENOS)在Thr495处的磷酸化，从而引起ROS释放和ONOO⁻的产生。D-4F通过AMPK/⁻途径抑制NADPH氧化酶的激活、ROS的产生和ONOO蛋白的形成。此外，在SD大鼠血管内注射碘化甘油后，虽然没有观察到明显的细胞凋亡和形态变化，但在动脉内皮细胞中诱导了显著的炎症反应。D-4F可减轻体内碘引起的血管炎症。综上所述，D-4F除了清除ROS外，还可以通过AMPK/PKC途径抑制ROS的产生和ONOO⁻的形成，从而减轻内皮细胞的氧化损伤。因此，D-4F可能成为预防CI-AKI的潜在药物。
Endothelial dysfunction is involved in the pathophysiological processes of contrast media (CM)–induced acute kidney injury (CI-AKI) after vascular angiography or intervention. Previous study found that apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, alleviates endothelial impairments via upregulating heme oxygenase-1 (HO-1) expression and scavenging excessively generated reactive oxygen species (ROS). However, whether D-4F could ameliorate oxidative injuries in endothelial cells through suppressing ROS production remains unclear. In this study, a representative nonionic iodinated CM, iodixanol, was chosen for the in vitro and in vivo studies. Endothelial cell viability was assayed using micrographs, lactate dehydrogenase (LDH) activity, and cell counting kit-8 (CCK-8). Apoptosis was detected using flow cytometry analysis and caspase-3 activation. Endothelial inflammation was tested using monocyte adhesion assay and adhesion molecule expression. ROS production was detected by measuring the formation of lipid peroxidation malondialdehyde (MDA) through the thiobarbituric acid reactive substance (TBARS) assay. Peroxynitrite (ONOO⁻) formation was tested using the 3-nitrotyrosine ELISA kit. Iodixanol impaired cell viability, promoted vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1) expression, and induced cell apoptosis in human umbilical vein endothelial cells (HUVECs). However, D-4F mitigated these injuries. Furthermore, iodixanol induced the phosphorylation of protein kinase C (PKC) beta II, p47, Rac1, and endothelial nitric oxide synthase (eNOS) at Thr495, which elicited ROS release and ONOO⁻ generation. D-4F inhibited NADPH oxidase (NOX) activation, ROS production, and ONOO⁻ formation via the AMP-activated protein kinase (AMPK)/PKC pathway. Additionally, after an intravascular injection of iodixanol in Sprague Dawley rats, iodixanol induced a remarkable inflammatory response in arterial endothelial cells, although significant apoptosis and morphological changes were not observed. D-4F alleviated the vessel inflammation resulting from iodixanol in vivo. Collectively, besides scavenging ROS, D-4F could also suppress ROS production and ONOO⁻ formation through the AMPK/PKC pathway, which ameliorated oxidative injuries in endothelial cells. Hence, D-4F might serve as a potential agent in preventing CI-AKI.
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DOI：
10.1161/atvbaha.109.187518
发表时间：
2010-02
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Navab M;Shechter I;Anantharamaiah GM;Reddy ST;Van Lenten BJ;Fogelman AM
通讯作者：
Fogelman AM
表没食子儿茶素-3-没食子酸酯靶向 HO-1 可通过抗氧化应激和抗炎途径减少造影剂引起的肾损伤
影响因子：
3.7
作者：
Gao Z;Han Y;Hu Y;Wu X;Wang Y;Zhang X;Fu J;Zou X;Zhang J;Chen X;Jose PA;Lu X;Zeng C
通讯作者：
Zeng C
DOI：
10.1152/ajpheart.00850.2012
发表时间：
2013-07-01
影响因子：
4.8
作者：
Baotic, Ines;Ge, Zhi-Dong;Kersten, Judy R.
通讯作者：
Kersten, Judy R.
影响因子：
5
作者：
Liu, Donghui;Ding, Zhenzhen;Wang, Yan
通讯作者：
Wang, Yan
影响因子：
3.3
作者：
Ou, Hsiu-Chung;Hsieh, Yueh-Ling;Lee, Shin-Da
通讯作者：
Lee, Shin-Da